Advertisement

Annals of Surgical Oncology

, Volume 26, Issue 13, pp 4673–4680 | Cite as

The Prognosis and Natural History of In-Transit Melanoma Metastases at a High-Volume Centre

  • Emilia Nan Tie
  • Lumine H. Na
  • Rodney J. Hicks
  • John Spillane
  • David Speakman
  • Michael A. Henderson
  • David E. GyorkiEmail author
Melanoma

Abstract

Background

Patients with in-transit melanoma metastases (ITM) experience a diverse spectrum of clinical presentations and a highly variable disease course. There is no standardized treatment protocol for these patients due to the limited data comparing treatment modalities for ITM. This is the first study to describe the disease trajectory and natural history of a large cohort of patients with ITM.

Methods

A retrospective study of patients treated for ITM between 2004 and 2018 at the Peter MacCallum Cancer Centre was performed. Clinical and pathological characteristics for primary and in-transit episodes were analyzed for predictors of relapse-free survival (RFS), distant metastasis-free survival (DMFS), and melanoma-specific survival.

Results

A total of 109 patients with 303 episodes of ITM were identified: 52 (48%) females, median age 70.1 years (range 35–92). The median RFS for all episodes was 5 months (95% confidence interval [CI] 4.2–5.7). Eighty-seven percent of episodes involving isolated in-transit lesions underwent surgical excision, compared with 17% involving more than five in-transit lesions. A trend was seen between a greater number of lesions and shorter RFS (p = 0.055). The median DMFS was 34.8 months (95% CI 22.8–51.6). Factors associated with shorter DMFS included primary tumor thickness (hazard ratio [HR] 1.08, 95% CI 1.01–1.15; p = 0.026), site of primary tumor (p = 0.008), and BRAF mutation (HR 2.12, 95% CI 1.14–3.94; p = 0.018).

Conclusions

Locoregional relapse is common in patients with ITM regardless of treatment modality. Characteristics of the ITM may predict for RFS, while primary tumor characteristics remain important predictors of DMFS.

Notes

Acknowledgment

Melanoma Research Victoria.

Funding

No sources of funding were used in the preparation of this study.

Disclosure

Emilia Nan Tie, Lumine H. Na, Rodney J. Hicks, John Spillane, David Speakman, Michael A. Henderson, and David E. Gyorki have no conflicts of interest to declare.

Supplementary material

10434_2019_7965_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 12 kb)

References

  1. 1.
    Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472–492.Google Scholar
  2. 2.
    Hayes AJ, Clark MA, Harries M, Thomas JM. Management of in-transit metastases from cutaneous malignant melanoma. Br J Surg. 2004;91(6):673–682.CrossRefGoogle Scholar
  3. 3.
    Pawlik TM, Ross MI, Johnson MM, et al. Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy. Ann Surg Oncol. 2005;12(8):587–596.CrossRefGoogle Scholar
  4. 4.
    Wong JH, Cagle LA, Kopald KH, Swisher SG, Morton DL. Natural history and selective management of in transit melanoma. J Surg Oncol. 1990;44(3):146–150.CrossRefGoogle Scholar
  5. 5.
    Read RL, Haydu L, Saw RP, et al. In-transit melanoma metastases: incidence, prognosis, and the role of lymphadenectomy. Ann Surg Oncol. 2015;22(2):475–481.CrossRefGoogle Scholar
  6. 6.
    Testori A, Ribero S, Bataille V. Diagnosis and treatment of in-transit melanoma metastases. Eur J Surg Oncol. 2017;43(3):544–560.CrossRefGoogle Scholar
  7. 7.
    Perone JA, Farrow N, Tyler DS, Beasley GM. Contemporary approaches to in-transit melanoma. J Oncol Pract. 2018;14(5):292–300.CrossRefGoogle Scholar
  8. 8.
    Thompson JF, Agarwala SS, Smithers BM, et al. Phase 2 study of intralesional PV-10 in refractory metastatic melanoma. Ann Surg Oncol. 2015;22(7):2135–2142.CrossRefGoogle Scholar
  9. 9.
    Lippey J, Bousounis R, Behrenbruch C, et al. Intralesional PV-10 for in-transit melanoma: a single-center experience. J Surg Oncol. 2016;114(3):380–384.CrossRefGoogle Scholar
  10. 10.
    Seegenschmiedt MH, Keilholz L, Altendorf-Hofmann A, et al. Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience. Int J Radiat Oncol Biol Phys. 1999;44(3):607–618.CrossRefGoogle Scholar
  11. 11.
    Kroon HM, Moncrieff M, Kam PC, Thompson JF. Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol. 2008;15(11):3003–3013.Google Scholar
  12. 12.
    Weber J, Mandala M, Del Vecchio M, et al. Adjuvant Nivolumab versus Ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–1835.CrossRefGoogle Scholar
  13. 13.
    Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377(19):1813–1823.CrossRefGoogle Scholar
  14. 14.
    Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378(19):1789–1801.CrossRefGoogle Scholar
  15. 15.
    Ascierto PA, McArthur GA, Dreno B, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016;17(9):1248–1260.CrossRefGoogle Scholar
  16. 16.
    Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345–1356.CrossRefGoogle Scholar
  17. 17.
    Long GV, Eroglu Z, Infante J, et al. Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib. J Clin Oncol. 2018;36(7):667–673.CrossRefGoogle Scholar
  18. 18.
    Weide B, Faller C, Buttner P, et al. Prognostic factors of melanoma patients with satellite or in-transit metastasis at the time of stage III diagnosis. PLoS ONE. 2013;8(4):e63137.CrossRefGoogle Scholar
  19. 19.
    Gassenmaier M, Eigentler TK, Keim U, et al. Serial or parallel metastasis of cutaneous melanoma? A study of the german central malignant melanoma registry. J Invest Dermatol. 2017;137(12):2570–2577.CrossRefGoogle Scholar
  20. 20.
    Ascierto PA, Kirkwood JM, Grob JJ, et al. The role of BRAF V600 mutation in melanoma. J Transl Med. 2012;10:85.CrossRefGoogle Scholar
  21. 21.
    Barbour AP, Tang YH, Armour N, et al. BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma: implications for melanoma staging and adjuvant therapy. Eur J Cancer. 2014;50(15):2668–2676.CrossRefGoogle Scholar
  22. 22.
    Dong XD, Tyler D, Johnson JL, DeMatos P, Seigler HF. Analysis of prognosis and disease progression after local recurrence of melanoma. Cancer. 2000;88(5):1063–1071.CrossRefGoogle Scholar
  23. 23.
    Dossett LA, Ben-Shabat I, Olofsson Bagge R, Zager JS. Clinical response and regional toxicity following isolated limb infusion compared with isolated limb perfusion for in-transit melanoma. Ann Surg Oncol. 2016;23(7):2330–2335.CrossRefGoogle Scholar
  24. 24.
    Kroon HM, Coventry BJ, Giles MH, et al. Australian Multicenter Study of Isolated Limb Infusion for Melanoma. Ann Surg Oncol. 2016;23(4):1096–1103.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Emilia Nan Tie
    • 1
    • 2
  • Lumine H. Na
    • 3
  • Rodney J. Hicks
    • 4
    • 5
  • John Spillane
    • 1
    • 2
  • David Speakman
    • 1
  • Michael A. Henderson
    • 1
    • 2
  • David E. Gyorki
    • 1
    • 2
    • 6
    Email author
  1. 1.Division of Cancer Surgery, Department of Surgical OncologyPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Department of SurgeryThe University of MelbourneMelbourneAustralia
  3. 3.Centre for Biostatistics and Clinical TrialsPeter MacCallum Cancer CentreMelbourneAustralia
  4. 4.Centre for Cancer ImagingPeter MacCallum Cancer CentreMelbourneAustralia
  5. 5.Department of Medicine/Sir Peter MacCallum Department of OncologyUniversity of MelbourneMelbourneAustralia
  6. 6.Victorian Comprehensive Cancer CentreMelbourneAustralia

Personalised recommendations